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Unexplained subfertility in RA linked to periconceptional NSAID use

Women with rheumatoid arthritis are more
often diagnosed with unexplained subfertility, compared with
women in the general population, according to a new study
published in Arthritis Care & Research.

Dr. Jenny Brouwer

Patrice Wendling/Frontline Medical News

“Fertility is compromised in women with
rheumatoid arthritis. In 36%-42% of female RA patients,
diagnosed before family completion, the time to pregnancy
exceeds 12 months, whereas in the general population, this
is only the case in 10%-17% of couples,” reported Jenny
Brouwer, MD, and her associates at Erasmus University
Medical Center, Rotterdam, the Netherlands (Arthritis Care
Res. 2016 Oct 4. doi: 10.1002/acr.23124).

In addition, when women with RA try to
conceive, their antirheumatic treatment regimens need to be
adjusted, which increases risk for permanent joint damage,
the investigators wrote, adding that “understanding the
underlying mechanisms of subfertility in RA, and treatment
of these mechanisms whenever possible, would be an important
step forward in the care for these patients.”

To study the outcome of fertility assessments
in women with RA and subfertility, Dr. Brouwer and her
associates performed a cross-sectional study of 260 female
RA patients who were recruited from the Pregnancy-induced
Amelioration of RA study, a Dutch nationwide prospective
observational trial of women diagnosed with RA who were in
their first trimester of pregnancy or who were trying to
conceive.

Each eligible participant received a
questionnaire that included questions regarding reproductive
history, time to pregnancy, mode of conception for prior
pregnancies, fertility assessments, and fertility
treatments. For the 178 (68%) women who returned completed
questionnaires, additional gynecologic histories and
diagnoses were collected from medical histories and/or
patient files.

Analysis of these data revealed that 82 women
(46%; 95% confidence interval, 39%-53%) with RA were
considered subfertile. Subfertility was most often
unexplained (48% of known diagnoses) or caused by
anovulation (28%) or semen abnormalities (16%).

“In comparison to the general population,
female RA patients appear to be more often diagnosed with
unexplained subfertility, whereas the percentage of
subfertile women with anovulation was equal or slightly
increased compared to percentages found in the general
population,” the investigators wrote.

The majority of subfertile RA patients
received fertility treatments, and “a considerable number of
all pregnancies were conceived after women had been treated
for subfertility,” according to the researchers.

The use of periconceptional NSAIDs may have
contributed to subfertility, based on a subanalysis. Nearly
half (48%) of women with unexplained subfertility used
NSAIDs periconceptionally, whereas only 17% of other
subfertile RA patients did so (P = .013). No other
disease-related factors, including disease activity and
periconceptional prednisone use, were significantly
associated with unexplained subfertility.

The significant association between
periconceptional NSAIDs use and unexplained subfertility “is
in concordance with a previous study within the PARA cohort
where we have shown that a longer [time to pregnancy] was
associated with the periconceptional use of NSAIDs,” Dr.
Brouwer and her associates wrote.

“In daily practice, when an RA patient
wishes to conceive, NSAIDs should be avoided, and early
consultation with an expert rheumatologist and a
fertility specialist should be considered to optimize
the patient’s chance of a complete family,” the
investigators recommended.